NCT01416428

Brief Summary

The purpose of this study is to determine the maximum tolerated dose (MTD), activity, and safety of oprozomib in patients with hematologic malignancies.

Trial Health

57
Monitor

Trial Health Score

Automated assessment based on enrollment pace, timeline, and geographic reach

Enrollment
210

participants targeted

Target at P75+ for phase_1 multiple-myeloma

Timeline
Completed

Started Oct 2011

Longer than P75 for phase_1 multiple-myeloma

Geographic Reach
1 country

19 active sites

Status
terminated

Health score is calculated from publicly available data and should be used for screening purposes only.

Trial Relationships

Click on a node to explore related trials.

Study Timeline

Key milestones and dates

First Submitted

Initial submission to the registry

August 11, 2011

Completed
4 days until next milestone

First Posted

Study publicly available on registry

August 15, 2011

Completed
2 months until next milestone

Study Start

First participant enrolled

October 15, 2011

Completed
4.8 years until next milestone

Primary Completion

Last participant's last visit for primary outcome

August 8, 2016

Completed
3 years until next milestone

Study Completion

Last participant's last visit for all outcomes

August 12, 2019

Completed
Last Updated

November 8, 2022

Status Verified

November 1, 2022

Enrollment Period

4.8 years

First QC Date

August 11, 2011

Last Update Submit

November 4, 2022

Conditions

Keywords

multiple myelomawaldenstrom macroglobulinemia

Outcome Measures

Primary Outcomes (1)

  • Determine the MTD (Phase 1) and ORR (Phase 2).

    Phase 1- Determine Maximum Tolerated Dose (MTD) with 3 + 3 Dose Escalation Cohorts in patients hematologic malignancies. Phase 2- The Phase 2 portion of this trial will enroll patients with Multiple Myeloma (MM) and Waldenstrom Macroglobulinemia (WM) into separate arms to assess activity of oprozomib in these patient groups. The purpose of the Phase 2 portion of the study is to estimate the best ORR (for each group separately).

    6 weeks to 18 months

Secondary Outcomes (17)

  • Evaluate the duration of response (DOR)

    64 months

  • Estimate the clinical benefit response (CBR)

    64 months

  • Estimate the major response for Waldenström macroglobulinemia (WM)

    64 months

  • Evaluate progression-free survival (PFS) for multiple myeloma (MM) subjects

    64 months

  • Evaluate the PFS for Waldenström macroglobulinemia (WM) subjects

    64 months

  • +12 more secondary outcomes

Study Arms (2)

QDx2 Dosing Schedule

EXPERIMENTAL

QDx2 is defined as patients receiving Oprozomib Tablets once daily on Days 1, 2, 8, and 9 of the 14-day cycle. The schedule will be evaluated in Phase 1 for MTD in patients with hematologic malignancies, and will also be evaluated in Phase 2 for ORR in patients with MM and WM.

Drug: oprozomib

QDx5 Dosing Schedule

EXPERIMENTAL

QDx5 is defined as patients receiving Oprozomib Tablets once daily on Days 1 to 5 of the 14-day cycle. The schedule will be evaluated in Phase 1 for MTD in patients with hematologic malignancies, and will also be evaluated in Phase 2 for ORR in patients with MM and WM.

Drug: oprozomib

Interventions

Patients enrolled will receive Oprozomib Tablets once daily either on Days 1-5 (QDx5 schedule) or on Days 1, 2, 8, and 9 (QDx2 weekly schedule) of the 14-day treatment cycle.

QDx2 Dosing ScheduleQDx5 Dosing Schedule

Eligibility Criteria

Age18 Years+
Sexall
Healthy VolunteersNo
Age GroupsAdult (18-64), Older Adult (65+)

You may qualify if:

  • Phase 1b
  • Histologically confirmed diagnosis of a hematologic malignancy, excluding patients with acute leukemia or MDS.
  • Relapsed after standard therapy for their malignancy and considered to be an appropriate candidate for a Phase 1 clinical study by their treating physician.
  • Phase 2
  • Multiple myeloma with measurable disease
  • Waldenström macroglobulinemia with symptomatic relapse
  • Eastern Cooperative Oncology Group (ECOG) Performance Status 0-2.
  • Ethical/Other
  • Patients must sign a written informed consent form in accordance with federal, local, and institutional guidelines.
  • Female patients of childbearing potential must have a negative serum or urine pregnancy test and agree to use effective contraception. Male patients must use an effective barrier method of contraception.

You may not qualify if:

  • Chemotherapy with approved or investigational anticancer therapeutics, including steroid therapy intended to treat underlying malignancy, within 3 weeks prior to first dose or 6 weeks for antibody therapy.
  • Radiation therapy within 3 weeks prior to first dose. Radioimmunotherapy within 8 weeks prior to first dose. Localized radiation therapy within 1 week prior to first dose.
  • Immunotherapy within 3 weeks prior to first dose (except for antibody therapy, where 6 weeks is required).
  • Prior stem cell transplant (SCT) therapy (autologous SCT within the prior 8 weeks; allogeneic SCT within the prior 16 weeks). Patients with prior allogeneic SCT should not have evidence of moderate-to-severe graft-vs-host disease (GvHD; as defined in Filipovich 2005).
  • Evidence of central nervous system (CNS) lymphoma.
  • Prior treatment with carfilzomib unless in the phase 2.
  • Major surgery within 3 weeks prior to first dose.
  • Symptomatic Congestive heart failure, ischemia, conduction abnormalities, or myocardial infarction within 6 months.
  • Acute active infection requiring systemic antibiotics, antivirals, or antifungals.
  • Known or suspected human immunodeficiency virus (HIV) infection or patients who are HIV seropositive.
  • Active hepatitis A, B, or C infection.
  • Significant neuropathy (Grade 3, Grade 4, or Grade 2 with pain) at the time of the first dose.
  • Patients with pleural effusions requiring routine thoracentesis or ascites requiring routine paracentesis.
  • History of previous clinically significant GI bleed in the last 6 months prior to first dose.
  • Female patients who are pregnant or lactating.

Contact the study team to confirm eligibility.

Sponsors & Collaborators

Study Sites (19)

Mayo Clinic Scottsdale

Scottsdale, Arizona, United States

Location

Pacific Cancer Care

Salinas, California, United States

Location

Colorado Blood Cancer Institute

Denver, Colorado, United States

Location

Mayo Clinic

Jacksonville, Florida, United States

Location

Winship Cancer Institute, Emory University

Atlanta, Georgia, United States

Location

Rush University Medical Center

Chicago, Illinois, United States

Location

University of Chicago Medical Center

Chicago, Illinois, United States

Location

University of Maryland, Greenebaum Cancer Center

Baltimore, Maryland, United States

Location

Dana Farber Cancer Institute

Boston, Massachusetts, United States

Location

Mass General Hospital

Boston, Massachusetts, United States

Location

Virginia Piper Cancer Institute

Minneapolis, Minnesota, United States

Location

Mayo Clinic

Rochester, Minnesota, United States

Location

Washington University School of Medicine Division of Oncology

St Louis, Missouri, United States

Location

John Theurer Cancer Center at Hackensack University

Hackensack, New Jersey, United States

Location

Hematology Oncology of Northern New Jersey

Morristown, New Jersey, United States

Location

New York Oncology Hematology

Albany, New York, United States

Location

Mount Sinai Medical Center

New York, New York, United States

Location

Sarah Cannon Research Institute / Tennessee Oncology, PLLC

Nashville, Tennessee, United States

Location

Columbia Basin Hematology and Oncology

Kennewick, Washington, United States

Location

Related Links

MeSH Terms

Conditions

Multiple MyelomaWaldenstrom Macroglobulinemia

Interventions

ONX 0912

Condition Hierarchy (Ancestors)

Neoplasms, Plasma CellNeoplasms by Histologic TypeNeoplasmsHemostatic DisordersVascular DiseasesCardiovascular DiseasesParaproteinemiasBlood Protein DisordersHematologic DiseasesHemic and Lymphatic DiseasesHemorrhagic DisordersLymphoproliferative DisordersImmunoproliferative DisordersImmune System DiseasesLymphatic Diseases

Study Officials

  • MD

    Amgen

    STUDY DIRECTOR

Study Design

Study Type
interventional
Phase
phase 1
Allocation
NON RANDOMIZED
Masking
NONE
Purpose
TREATMENT
Intervention Model
PARALLEL
Sponsor Type
INDUSTRY
Responsible Party
SPONSOR

Study Record Dates

First Submitted

August 11, 2011

First Posted

August 15, 2011

Study Start

October 15, 2011

Primary Completion

August 8, 2016

Study Completion

August 12, 2019

Last Updated

November 8, 2022

Record last verified: 2022-11

Locations